Disorders of Human Coenzyme Q10 Metabolism: An Overview

Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extramitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant, plays an important role in fatty acid, pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. In view of the central role of CoQ10 in cellular metabolism, it is unsurprising that a CoQ10 deficiency is linked to the pathogenesis of a range of disorders. CoQ10 deficiency is broadly classified into primary or secondary deficiencies. Primary deficiencies result from genetic defects in the multi-step biochemical pathway of CoQ10 synthesis, whereas secondary deficiencies can occur as result of other diseases or certain pharmacotherapies. In this article we have reviewed the clinical consequences of primary and secondary CoQ10 deficiencies, as well as providing some examples of the successful use of CoQ10 supplementation in the treatment of disease

Coenzyme Q10, Ageing and the Nervous System: An Overview

The ageing brain is characterised by changes at the physical, histological, biochemical and physiological levels. This ageing process is associated with an increased risk of developing a number of neurological disorders, notably Alzheimer’s disease and Parkinson’s disease. There is evidence that mitochondrial dysfunction and oxidative stress play a key role in the pathogenesis of such disorders. In this article, we review the potential therapeutic role in these age-related neurological disorders of supplementary coenzyme Q10, a vitamin-like substance of vital importance for normal mitochondrial function and as an antioxidant. This review is concerned primarily with studies in humans rather than in vitro studies or studies in animal models of neurological disease. In particular, the reasons why the outcomes of clinical trials supplementing coenzyme Q10 in these neurological disorders is discussed

Fluorescent characterization of differentiated myotubes using flow cytometry

Flow cytometry is routinely used in the assessment of skeletal muscle progenitor cell (myoblast) populations. However, a full gating strategy, inclusive of difficult to interpret forward and side scatter data, which documents cytometric analysis of differentiated myoblasts (myotubes) has not been reported. Beyond changes in size and shape, there are substantial metabolic and protein changes in myotubes allowing for their potential identification within heterogenous cell suspensions. To establish the utility of flow cytometry for determination of myoblasts and myotubes, C2C12 murine cell populations were assessed for cell morphology and metabolic reprogramming. Laser scatter, both forward (FSC; size) and side (SSC; granularity), measured cell morphology, while mitochondrial mass, reactive oxygen species (ROS) generation and DNA content were quantified using the fluorescent probes, MitoTracker green, CM-H2DCFDA and Vybrant DyeCycle, respectively. Immunophenotyping for myosin heavy chain (MyHC) was utilized to confirm myotube differentiation. Cellular viability was determined using Annexin V/propidium iodide dual labelling. Fluorescent microscopy was employed to visualize fluorescence and morphology. Myotube and myoblast populations were resolvable through non-intuitive interpretation of laser scatter-based morphology assessment and mitochondrial mass and activity assessment. Myotubes appeared to have similar sizes to the myoblasts based on laser scatter but exhibited greater mitochondrial mass (159%, p < 0.0001), ROS production (303%, p < 0.0001), DNA content (18%, p < 0.001) and expression of MyHC (147%, p < 0.001) compared to myoblasts. Myotube sub-populations contained a larger viable cluster of cells which were unable to be fractionated from myoblast populations and a smaller population cluster which likely contains apoptotic bodies. Imaging of differentiated myoblasts that had transited through the flow cytometer revealed the presence of intact, ‘rolled-up’ myotubes, which would alter laser scatter properties and potential transit through the laser beam. Our results indicate that myotubes can be analyzed successfully using flow cytometry. Increased mitochondrial mass, ROS and DNA content are key features that correlate with MyHC expression but due to myotubes ‘rolling up’ during flow cytometric analysis, laser scatter determination of size is not positively correlated; a phenomenon observed with some size determination particles and related to surface properties of said particles. We also note a greater heterogeneity of myotubes compared to myoblasts as evidenced by the 2 distinct sub-populations. We suggest that acoustic focussing may prove effective in identifying myotube sub populations compared to traditional hydrodynamic focussing

Biology of a new virus isolated from Lupinus nootkatensis plants in Alaska

A new virus named Nootka lupine vein-clearing virus (NLVCV) was isolated from Lupinus nootkatensis plants that were confined to a relatively small area in the Talkeetna mountains of south-central Alaska. Annual surveys (2000–03) consistently found leaf symptoms of pronounced vein clearing and mosaic on 3- to 4-week-old plants in late June. Spherical particles ≈ 30 nm in diameter were isolated from these leaves. Virions contained a single-stranded RNA of ≈ 4·0–4·2 kb and one species of capsid protein estimated to be ≈ 40 kDa. The double-stranded RNA profile from naturally infected leaves consisted of three major bands ≈ 4·2, 1·9 and 1·5 kbp. Protein extractions from either sap or virions of diseased plants reacted to polyclonal antiserum made against the virions in Western blot assays. A predicted PCR product ≈ 500 bp was synthesized from virion RNA using primers specific to the carmovirus RNA-dependent RNA polymerase (RDRP) gene. The nucleotide sequence of the amplified DNA did not match any known virus, but contained short regions of identity to several carmoviruses. Only species belonging to the Fabaceae were susceptible to NLVCV by mechanical inoculation. Based on dsRNA profile, size of virion RNA genome and capsid protein, and similarity of the RDRP gene to that of other carmoviruses, it is suggested that NLVCV is a member of the family Tombusviridae , and tentatively of the genus Carmovirus . As the host range, RDRP gene and dsRNA profile of NLVCV are different from those of known viruses, this is a newly described plant virus

Glucanocellulosic ethanol: The undiscovered biofuel potential in energy crops and marine biomass

Converting biomass to biofuels is a key strategy in substituting fossil fuels to mitigate climate change. Conventional strategies to convert lignocellulosic biomass to ethanol address the fermentation of cellulose-derived glucose. Here we used super-resolution fluorescence microscopy to uncover the nanoscale structure of cell walls in the energy crops maize and Miscanthus where the typical polymer cellulose forms an unconventional layered architecture with the atypical (1, 3)-β-glucan polymer callose. This raised the question about an unused potential of (1, 3)-β-glucan in the fermentation of lignocellulosic biomass. Engineering biomass conversion for optimized (1, 3)-β-glucan utilization, we increased the ethanol yield from both energy crops. The generation of transgenic Miscanthus lines with an elevated (1, 3)-β-glucan content further increased ethanol yield providing a new strategy in energy crop breeding. Applying the (1, 3)-β-glucan-optimized conversion method on marine biomass from brown macroalgae with a naturally high (1, 3)-β-glucan content, we not only substantially increased ethanol yield but also demonstrated an effective co-fermentation of plant and marine biomass. This opens new perspectives in combining different kinds of feedstock for sustainable and efficient biofuel production, especially in coastal regions

Thermochemistry of Microhydration of Sodiated and Potassiated Monosaccharides

The thermochemical properties ΔHon , ΔSon, and ΔGon for the hydration of sodiated and potassiated monosaccharides (Ara = arabinose, Xyl = xylose, Rib = ribose, Glc = glucose, and Gal = galactose) have been experimentally studied in the gas phase at 10 mbar by equilibria measurements using an electrospray high-pressure mass spectrometer equipped with a pulsed ion beam reaction chamber. The hydration enthalpies for sodiated complexes were found to be between −46.4 and −57.7 kJ/mol for the first, and −42.7 and −52.3 kJ/mol for the second water molecule. For potassiated complexes, the water binding enthalpies were similar for all studied systems and varied between −48.5 and −52.7 kJ/mol. The thermochemical values for each system correspond to a mixture of the α and β anomeric forms of monosaccharide structures involved in their cationized complexes

Tracing Cattle Breeds with Principal Components Analysis Ancestry Informative SNPs

The recent release of the Bovine HapMap dataset represents the most detailed survey of bovine genetic diversity to date, providing an important resource for the design and development of livestock production. We studied this dataset, comprising more than 30,000 Single Nucleotide Polymorphisms (SNPs) for 19 breeds (13 taurine, three zebu, and three hybrid breeds), seeking to identify small panels of genetic markers that can be used to trace the breed of unknown cattle samples. Taking advantage of the power of Principal Components Analysis and algorithms that we have recently described for the selection of Ancestry Informative Markers from genomewide datasets, we present a decision-tree which can be used to accurately infer the origin of individual cattle. In doing so, we present a thorough examination of population genetic structure in modern bovine breeds. Performing extensive cross-validation experiments, we demonstrate that 250-500 carefully selected SNPs suffice in order to achieve close to 100% prediction accuracy of individual ancestry, when this particular set of 19 breeds is considered. Our methods, coupled with the dense genotypic data that is becoming increasingly available, have the potential to become a valuable tool and have considerable impact in worldwide livestock production. They can be used to inform the design of studies of the genetic basis of economically important traits in cattle, as well as breeding programs and efforts to conserve biodiversity. Furthermore, the SNPs that we have identified can provide a reliable solution for the traceability of breed-specific branded products

How are time-dependent childbearing intentions realized? Realization, postponement, abandonment, bringing forward

Our study aims to identify factors that facilitate or inhibit the realization of fertility intentions. The analysis uses data collected in the first two waves of a Hungarian longitudinal survey. Fertility intentions recorded at the first wave pertain to the subsequent 3-year period, just similar to the behavior variable measuring the realization of intentions, i.e., a birth within the 3-year period in question. For this analysis, we used the respondents’ demographic, socio-structural, and orientational traits recorded at the first interview. Our findings show that age, parity, and partnership play a determining role in the realization of fertility intentions, but employment status, religious affiliation, and overall life satisfaction all exhibit significant effects. A marked gender difference was detected not only with regard to employment status but in the area of values and orientations as well.L’objectif de notre étude est d’identifier les facteurs qui facilitent ou inhibent la réalisation des intentions de fécondité. L’analyse s’appuie sur les deux premières vagues d’une enquête longitudinale menée en Hongrie. Les intentions de fécondité recueillies dans le cadre de la première vague concernent la période des trois années à venir, de la même façon que la variable de comportement mesurant la réalisation des intentions, à savoir, une naissance survenue au cours de cette même période. Les caractéristiques démographiques et socio-structurelles, de même que certaines dispositions personnelles recueillies lors du premier entretien ont été utilisées dans l’analyse. Nos résultats indiquent qu’à la fois l’âge, la parité, et la situation de couple jouent un rôle capital dans la réalisation des intentions et aussi que la situation d’emploi, l’appartenance religieuse et le niveau de satisfaction par rapport à la vie exercent une influence significative. Une différence prononcée entre hommes et femmes est mise en évidence en matière de situation d’emploi et également dans le domaine des valeurs et des dispositions personnelles

The impact of a team-based intervention on the lifestyle risk factor management practices of community nurses: outcomes of the community nursing SNAP trial

BackgroundLifestyle risk factors like smoking, nutrition, alcohol consumption, and physical inactivity (SNAP) are the main behavioural risk factors for chronic disease. Primary health care is an appropriate setting to address these risk factors in individuals. Generalist community health nurses (GCHNs) are uniquely placed to provide lifestyle interventions as they see clients in their homes over a period of time. The aim of the paper is to examine the impact of a service-level intervention on the risk factor management practices of GCHNs.MethodsThe trial used a quasi-experimental design involving four generalist community nursing services in NSW, Australia. The services were randomly allocated to either an intervention group or control group. Nurses in the intervention group were provided with training and support in the provision of brief lifestyle assessments and interventions. The control group provided usual care. A sample of 129 GCHNs completed surveys at baseline, 6 and 12&thinsp;months to examine changes in their practices and levels of confidence related to the management of SNAP risk factors. Six semi-structured interviews and four focus groups were conducted among the intervention group to explore the feasibility of incorporating the intervention into everyday practice.ResultsNurses in the intervention group became more confident in assessment and intervention over the three time points compared to their control group peers. Nurses in the intervention group reported assessing physical activity, weight and nutrition more frequently, as well as providing more brief interventions for physical activity, weight management and smoking cessation. There was little change in referral rates except for an improvement in weight management related referrals. Nurses&rsquo; perception of the importance of &lsquo;client and system-related&rsquo; barriers to risk factor management diminished over time.ConclusionsThis study shows that the intervention was associated with positive changes in self-reported lifestyle risk factor management practices of GCHNs. Barriers to referral remained. The service model needs to be adapted to sustain these changes and enhance referral